The Magnetic Stimulator Apparatus
Magnetic stimulation of neurons has been heavily investigated over the last decade. Almost all magnetic stimulation work has been done in vivo. The bulk of the magnetic stimulation work has been in the area of brain stimulation.
Cohen has been a rather large contributor to this field of research (See e.g., T. Kujirai, M. Sato, J. Rothwell, and L. G. Cohen, "The Effects of Transcranial Magnetic Stimulation on Median Nerve Somatosensory Evoked Potentials", Journal of Clinical Neurophysiology and Electro Encephalography, Vol. 89, No. 4, 1993, pps. 227-234, the disclosure of which is fully incorporated herein by reference.) This work has been accompanied by various other research efforts including that of Davey, et al. and that of Epstein (See, K. R. Davey, C. H. Cheng, C. M. Epstein "An Alloy--Core Electromagnet for Transcranial Brain Stimulation", Journal of Clinical Neurophysiology, Volume 6, Number 4, 1989; and, Charles Epstein, Daniel Schwartzberg, Kent Davey, and David Sudderth, "Localizing the Site of Magnetic Brain Stimulation in Humans", Neurology, Volume 40, April 1990, pps. 666-670, the disclosures of which are fully incorporated herein by reference).
Generally, the magnetic stimulation research has used air type coils in their stimulators. These coils are so named due to the fact that they lack a magnetic core. A well known producer of such coils is Cadwell, which produces a variety of different models. One of the goals of the present inventors has been to provide magnetic stimulator devices for use in a variety of applications, which are improvements over the devices previously used in the art. In our prior pending patent application, U.S. patent application Ser. No. 08/345,572, filed Nov. 28, 1994, which is the parent to the present application (the disclosure of which is fully incorporated herein by reference), a variety of such devices were disclosed for the use in peripheral nerve stimulation. Accordingly, it is an object of the present inventors herein to provide further devices for use in central nervous system stimulation in general, and transcranial brain stimulation in particular.
The Treatment of Depression
Transcranial magnetic stimulation is known to non-invasively alter the function of the cerebral cortex. (See e.g., George M S, Wassermann E M, Post R M, Transcranial magnetic stimulation: A neuropsychiatric tool for the 21st century, J. Neuropsychiatry, 1996; 8: 373-382, the disclosure of which is fully incorporated herein by reference). The magnetic fields used are generally generated by large, rapidly-changing currents passing through a wire coil on the scalp. Two recent studies have suggested that rapid rate transcranial magnetic stimulation (rTMS) may be used for exploring the functional neuroanatomy of emotions: healthy volunteers who received left pre-frontal stimulation reported an increase in self-rated sadness, while, in contrast, right pre-frontal stimulation caused an increase in happiness. (See, Pascual-Leone A., Catala M D, Pascual A P, Lateralized effect of rapid rate transcranial magnetic stimulation of the prefrontal cortex on mood, Neurology, 1996; 46: 499-502; and, George M S, Wasserman E M, Williams W., et al., Changes in mood and hormone levels after rapid-rate transcranial magnetic stimulation of the prefrontal cortex, J. Neuropsychiatry Clin. Neurosci. 1996; 8: 172-180, the disclosures of which are fully incorporated herein by reference.)
Other reports have begun to delineate the therapeutic use of rTMS in depression. The earliest such studies used round, non-focal coils centered at the cranial vertex, with stimulation rates well under 1 Hertz (Hz). Results were promising but not always statistically significant. (See, Hoflich G., Kasper S. Hufnagel A. et al., Application of transcranial magnetic stimulation in treatment of drug-resistant major depression: a report of two cases, Human Psychopharmacology, 1993; 8: 361-365; Grisaru N., Yarovslavsky U., Abarbanel J., et al., Transcranial magnetic stimulation in depression and schizophrenia, Eur. Neuropsychophannacol. 1994; 4: 287-288; and, Kilbinger H M, Hofllich G., Hufnagel A., et al., Transcranial magnetic stimulation (TMS) in the treatment of major depression: A pilot study, Human Psychopharmacology, 1995; 10: 305-310, the disclosures of which are fully incorporated herein by reference.)
Subsequently, George et al., described striking improvement in some depressed patients from treatment with rTMS over the left pre-frontal cortex. (See, George M S, Wasserman E M, Williams W A, et al., Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression, NeuroReport, 1995; 6: 1853-1856; and, George M S, Wasserman E M, Williams W E, Kimbrell T A, Little J T, Hallett M., Post R M, Daily left prefrontal rTMS improves mood in outpatient depression: a double blind placebo-controlled crossover trial, Am. J. Psychaitry, 1997 (in press), the disclosures of which are fully incorporated herein by reference). The largest such study to date was reported by Pascual-Leone et al., who used a five-month double blind placebo-controlled cross over design with five different treatment conditions. (See, Pascual-Leone A., Rubio B., Pallardo F. Catala M D, Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression, The Lancet, 1996; 348: 233-237, the disclosure of which is fully incorporated herein by reference.) Left pre-frontal rTMS was uniquely effective in 11 of 17 young (less than 60 years of age) psychotically depressed and medication resistant patients.
Accordingly, further to the work which has been done thus far in this field, it is also a goal of the present inventors to provide improved apparatus and methods for transcranial magnetic stimulation, and for the treatment of depression using such stimulation, as described more fully hereafter.
The Localization of Speech Arrest
With respect to the methods previously used for the localization of speech arrest, active localization of language function has traditionally been possible only with invasive procedures. The dominant hemisphere can be determined using the intracarotid amobarbital or Wada test. Cortical areas critical to language can be mapped using electrocorticography in the operating room, (See e.g. Penfield, 1950, cited below) or extra-operatively through electrode grids implanted in the subdural space. (See e.g. Lesser, 1987, cited below). The Wada test and electrocorticography have contributed greatly to our current understanding of language organization. However, because of their complexity and potential morbidity, these techniques are confined almost entirely to patients undergoing surgery for intractable epilepsy.
In the past decade, positron emission tomography and functional magnetic resonance imaging have shown promising results for language localization. But these newer imaging technologies requite complex and expensive equipment, and have other limitations in the form of poor temporal resolution or a restricted test environment. The correlation between the degree of metabolic change in different brain areas and their importance for a given cognitive task remains unknown. (See e.g., Ojemann, cited below).
At least four groups have reported lateralized speech arrest using rapid-rate transcranial magnetic brain stimulation (rTMS) in epilepsy patients. (See e.g., Pascual-Leone, 1991, Michelucci, 1994, Jennum, 1994, and Epstein, 1996, cited below). The results showed a high correlation with the Wada test, but sensitivity in the two largest series was only 50-67% (See, e.g., Jennum, 1994, and Michelucci, 1994, cited below). Most of these studies used large circular magnetic coils, along with stimulus parameters that may carry a risk of inducing seizures. (See, e.g. Pascual-Leone, 1993, cited below). Thus, the initial rTMS techniques were not optimal for detailed localization or for studies involving normal subjects.
Consequently, further to the work which has previously been done, it is also a goal of the present inventors to provide improved apparatus and methods for localization and characterization of brain function. As described hereafter, we recently described modifications of rTMS that produce lateralized speech arrest with reduced discomfort, a repetition rate as low as four Hertz, and a combination of stimulus parameters that comply with recent recommendations for safety in rTMS (See also, Epstein C M, Lah J J, Meador K, Weissman J D, Gaitain L E, Dihenia B, Optimum stimulus parameters for lateralized suppression of speech with magnetic brain stimulation, Neurology, 47: 1590-1593 (December 1996), the disclosure of which is fully incorporated herein by reference). The technique is useful for detailed studies of magnetic speech arrest in normal individuals.